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. 1995 May;69(5):3167–3170. doi: 10.1128/jvi.69.5.3167-3170.1995

Change in tropism upon immune escape by human immunodeficiency virus.

A McKnight 1, R A Weiss 1, C Shotton 1, Y Takeuchi 1, H Hoshino 1, P R Clapham 1
PMCID: PMC189019  PMID: 7707545

Abstract

The V3 loop of human immunodeficiency virus type 1 is both a determinant of viral cell tropism and a target for neutralizing antibodies. This relationship was investigated. Selection of a dual-tropic (T cells and macrophages) virus to replicate in CD4+ brain cells results in loss of macrophage tropism and of neutralization by an anti-V3 loop monoclonal antibody. Moreover, selection of the brain-selected variant to escape from V3 loop-specific neutralizing monoclonal antibodies results in the reduction or loss of brain cell tropism and the reacquisition of macrophage tropism. These data may indicate that the antigenic diversification of human immunodeficiency virus type 1 apparent after seroconversion can be selected either by immune responses or by colonization of new cell types.

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Selected References

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  1. Arendrup M., Nielsen C., Hansen J. E., Pedersen C., Mathiesen L., Nielsen J. O. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies. J Acquir Immune Defic Syndr. 1992;5(3):303–307. [PubMed] [Google Scholar]
  2. Asjö B., Morfeldt-Månson L., Albert J., Biberfeld G., Karlsson A., Lidman K., Fenyö E. M. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660–662. [PubMed] [Google Scholar]
  3. Boyd M. T., Simpson G. R., Cann A. J., Johnson M. A., Weiss R. A. A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. J Virol. 1993 Jun;67(6):3649–3652. doi: 10.1128/jvi.67.6.3649-3652.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chesebro B., Buller R., Portis J., Wehrly K. Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. J Virol. 1990 Jan;64(1):215–221. doi: 10.1128/jvi.64.1.215-221.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clapham P. R., Blanc D., Weiss R. A. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus. Virology. 1991 Apr;181(2):703–715. doi: 10.1016/0042-6822(91)90904-P. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clapham P. R., McKnight A., Weiss R. A. Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4. J Virol. 1992 Jun;66(6):3531–3537. doi: 10.1128/jvi.66.6.3531-3537.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Connor R. I., Mohri H., Cao Y., Ho D. D. Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol. 1993 Apr;67(4):1772–1777. doi: 10.1128/jvi.67.4.1772-1777.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis D., Stephens D. M., Carne C. A., Lachmann P. J. Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope. J Gen Virol. 1993 Dec;74(Pt 12):2609–2617. doi: 10.1099/0022-1317-74-12-2609. [DOI] [PubMed] [Google Scholar]
  9. Delassus S., Cheynier R., Wain-Hobson S. Nonhomogeneous distribution of human immunodeficiency virus type 1 proviruses in the spleen. J Virol. 1992 Sep;66(9):5642–5645. doi: 10.1128/jvi.66.9.5642-5645.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Domingo E., Díez J., Martínez M. A., Hernández J., Holguín A., Borrego B., Mateu M. G. New observations on antigenic diversification of RNA viruses. Antigenic variation is not dependent on immune selection. J Gen Virol. 1993 Oct;74(Pt 10):2039–2045. doi: 10.1099/0022-1317-74-10-2039. [DOI] [PubMed] [Google Scholar]
  11. Epstein L. G., Kuiken C., Blumberg B. M., Hartman S., Sharer L. R., Clement M., Goudsmit J. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology. 1991 Feb;180(2):583–590. doi: 10.1016/0042-6822(91)90072-j. [DOI] [PubMed] [Google Scholar]
  12. Evans L. A., McHugh T. M., Stites D. P., Levy J. A. Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol. 1987 May 15;138(10):3415–3418. [PubMed] [Google Scholar]
  13. Fung M. S., Sun C. R., Gordon W. L., Liou R. S., Chang T. W., Sun W. N., Daar E. S., Ho D. D. Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120. J Virol. 1992 Feb;66(2):848–856. doi: 10.1128/jvi.66.2.848-856.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  15. Goudsmit J., Debouck C., Meloen R. H., Smit L., Bakker M., Asher D. M., Wolff A. V., Gibbs C. J., Jr, Gajdusek D. C. Human immunodeficiency virus type 1 neutralization epitope with conserved architecture elicits early type-specific antibodies in experimentally infected chimpanzees. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4478–4482. doi: 10.1073/pnas.85.12.4478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. doi: 10.1126/science.1905842. [DOI] [PubMed] [Google Scholar]
  17. Koito A., Harrowe G., Levy J. A., Cheng-Mayer C. Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization. J Virol. 1994 Apr;68(4):2253–2259. doi: 10.1128/jvi.68.4.2253-2259.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsushita S., Robert-Guroff M., Rusche J., Koito A., Hattori T., Hoshino H., Javaherian K., Takatsuki K., Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. doi: 10.1128/jvi.62.6.2107-2114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Matthews T. J., Langlois A. J., Robey W. G., Chang N. T., Gallo R. C., Fischinger P. J., Bolognesi D. P. Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9709–9713. doi: 10.1073/pnas.83.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McKeating J. A., Gow J., Goudsmit J., Pearl L. H., Mulder C., Weiss R. A. Characterization of HIV-1 neutralization escape mutants. AIDS. 1989 Dec;3(12):777–784. doi: 10.1097/00002030-198912000-00001. [DOI] [PubMed] [Google Scholar]
  21. McKeating J. A., Shotton C., Cordell J., Graham S., Balfe P., Sullivan N., Charles M., Page M., Bolmstedt A., Olofsson S. Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120. J Virol. 1993 Aug;67(8):4932–4944. doi: 10.1128/jvi.67.8.4932-4944.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  23. Nara P., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Krone W., Goudsmit J. Evidence for rapid selection and deletion of HIV-1 subpopulations in vivo by V3-specific neutralizing antibody: a model of humoral-associated selection. Dev Biol Stand. 1990;72:315–341. [PubMed] [Google Scholar]
  24. Nowak M., May R. M. AIDS pathogenesis: mathematical models of HIV and SIV infections. AIDS. 1993;7 (Suppl 1):S3–18. [PubMed] [Google Scholar]
  25. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pang S., Vinters H. V., Akashi T., O'Brien W. A., Chen I. S. HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J Acquir Immune Defic Syndr. 1991;4(11):1082–1092. [PubMed] [Google Scholar]
  27. Power C., McArthur J. C., Johnson R. T., Griffin D. E., Glass J. D., Perryman S., Chesebro B. Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences. J Virol. 1994 Jul;68(7):4643–4649. doi: 10.1128/jvi.68.7.4643-4649.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roos M. T., Lange J. M., de Goede R. E., Coutinho R. A., Schellekens P. T., Miedema F., Tersmette M. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection. J Infect Dis. 1992 Mar;165(3):427–432. doi: 10.1093/infdis/165.3.427. [DOI] [PubMed] [Google Scholar]
  29. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  30. Schuitemaker H., Koot M., Kootstra N. A., Dercksen M. W., de Goede R. E., van Steenwijk R. P., Lange J. M., Schattenkerk J. K., Miedema F., Tersmette M. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol. 1992 Mar;66(3):1354–1360. doi: 10.1128/jvi.66.3.1354-1360.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shimizu N. S., Shimizu N. G., Takeuchi Y., Hoshino H. Isolation and characterization of human immunodeficiency virus type 1 variants infectious to brain-derived cells: detection of common point mutations in the V3 region of the env gene of the variants. J Virol. 1994 Sep;68(9):6130–6135. doi: 10.1128/jvi.68.9.6130-6135.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shioda T., Levy J. A., Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
  33. Shioda T., Oka S., Ida S., Nokihara K., Toriyoshi H., Mori S., Takebe Y., Kimura S., Shimada K., Nagai Y. A naturally occurring single basic amino acid substitution in the V3 region of the human immunodeficiency virus type 1 env protein alters the cellular host range and antigenic structure of the virus. J Virol. 1994 Dec;68(12):7689–7696. doi: 10.1128/jvi.68.12.7689-7696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Takeuchi Y., Akutsu M., Murayama K., Shimizu N., Hoshino H. Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. J Virol. 1991 Apr;65(4):1710–1718. doi: 10.1128/jvi.65.4.1710-1718.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weiss R. A., Clapham P. R., Weber J. N., Dalgleish A. G., Lasky L. A., Berman P. W. Variable and conserved neutralization antigens of human immunodeficiency virus. Nature. 1986 Dec 11;324(6097):572–575. doi: 10.1038/324572a0. [DOI] [PubMed] [Google Scholar]
  36. Weiss R. A. How does HIV cause AIDS? Science. 1993 May 28;260(5112):1273–1279. doi: 10.1126/science.8493571. [DOI] [PubMed] [Google Scholar]
  37. Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wolfs T. F., Zwart G., Bakker M., Goudsmit J. HIV-1 genomic RNA diversification following sexual and parenteral virus transmission. Virology. 1992 Jul;189(1):103–110. doi: 10.1016/0042-6822(92)90685-i. [DOI] [PubMed] [Google Scholar]
  39. Zhang L. Q., MacKenzie P., Cleland A., Holmes E. C., Brown A. J., Simmonds P. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol. 1993 Jun;67(6):3345–3356. doi: 10.1128/jvi.67.6.3345-3356.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]

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